Bicuculline is a natural isoquinoline alkaloid that works as a gamma-aminobutyric acid receptor antagonist. It is widely found in Papaveraceae plants used in traditional Chinese medicines. Bicuculline not only has been shown to have favorable analgesic, memory-improving, and anxiolytic effects but may also cause adverse effects such as convulsions and epilepsy. A simple, rapid, and sensitive method was developed and validated for the determination of bicuculline in the plasma and tissue samples in rats by ultra-high-performance liquid chromatography–tandem mass spectrometry (MS/MS). The chromatographic separation was performed on a Thermo Scientific C18 column. The MS/MS system was operated in the positive multiple reaction monitoring mode, and the precursor–product ion transitions were optimized as m/z 368.0 → 307.1 for bicuculline and as 354.1 → 188.1 for protopine (internal standard). The linearity, accuracy, precision, recovery, and matrix effect were within acceptable limits. The experimental data showed that bicuculline was rapidly absorbed and eliminated in rats, with a moderate plasma protein binding ratio and low bioavailability. The main tissues of distribution were the kidney, liver, and brain; bicuculline could exert its pharmacological effects across the blood–brain barrier. This study has positive implications for the clinical use of herbal medicines containing bicuculline and for further development.

中文翻译：

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超高效液相色谱-串联质谱法研究荷包牡丹碱在大鼠胃和静脉给药后的药代动力学、组织分布和血浆蛋白结合率


Bicuculline 是一种天然异喹啉生物碱，可作为 γ-氨基丁酸受体拮抗剂。它广泛存在于用于中药的罂粟科植物中。荷包牡丹碱不仅被证明具有良好的镇痛、改善记忆和抗焦虑作用，而且还可能引起抽搐和癫痫等不良反应。开发并验证了一种简单、快速、灵敏的方法，用于通过超高效液相色谱-串联质谱 (MS/MS) 测定大鼠血浆和组织样品中的荷包牡丹碱。色谱分离在 Thermo Scientific C18 柱上进行。 MS/MS 系统在正多反应监测模式下运行，前体-产物离子转变优化为荷包牡丹碱的m/z 368.0 → 307.1，原托品（内标）优化为 354.1 → 188.1。线性、准确度、精密度、回收率和基质效应均在可接受的范围内。实验数据表明，荷包牡丹碱在大鼠体内吸收和消除迅速，血浆蛋白结合率适中，生物利用度较低。主要分布组织为肾、肝、脑；荷包牡丹碱可以穿过血脑屏障发挥其药理作用。本研究对于荷包牡丹碱中药的临床应用及进一步开发具有积极意义。